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1.
Mar Environ Res ; 193: 106287, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38101203

RESUMO

Based on the data of three CTD sections in the northern, northeastern and western Bering Sea of 2019 voyage of Chinese National Arctic Research Expedition (CHINARE), this paper analyzes and studies the hydrological characteristics of the water mass distribution, layered structure, and cline characteristics in different sea areas of the Bering Sea. The results indicate that the hydrological characteristics of the Bering Sea in the summer of 2019 are different from those in the past and that the water mass is warming in many locations. The maximum water temperature reaches 11.13 °C, and the maximum thickness of the warm water is about 32 m. The water mass composition and characteristics of the north-northeast-west sections are significantly different: the BL section has the highest salinity, while the BS section has the lowest salinity, and both the lowest temperature and the largest temperature variation appear in the BL section. The stratification characteristics in all sea areas are noteworthy. In the deep-water seas, there are three types of water masses: upper water (BSW), middle water (BIW) and deep water (BDW) from top to bottom, while two main water masses appear in the shelf waters with the Alaska Coastal Water (ACW) overlies the Bering Sea Shelf Water (BSW). Along the Bering Sea Slope Current (BSC), the water mass is essentially steady. Statically unstable hydrological inversion structure appears near the bottom of the three stations at the northern end of the BL section.


Assuntos
Água do Mar , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Água , Temperatura , Temperatura Baixa , Regiões Árticas
2.
PhytoKeys ; 230: 271-287, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37637214

RESUMO

Hedyotislongiramulissp. nov. (Rubiaceae) is described from Guangdong Province, China. It is similar to H.caudatifolia but differs in having puberulent, more or less tetragonal and decussately sulcate juvenile stems, waxy leaf surface, short inflorescence peduncles, high length ratio of corolla lobe to tube, and subglobose capsules. The phylogenetic analysis reveals that H.longiramulis is sister to H.pubirachis. Dimorphism concerning pollen size was observed in the heterostylous flowers. The complete chloroplast genome of the new species comprises a typical quadripartite structure of 153,616 bp in length, with two inverted repeats of 25,457 bp, a large single-copy of 85,050 bp and a small single-copy of 17,652 bp. It contains 112 unique genes, including 79 protein-coding genes, 29 tRNA genes, and four rRNA genes, the GC content of the chloroplast genome is 32.4%. The new species is provisionally evaluated as "Least Concern" because it is common and well-protected in two Provincial Nature Reserves.

3.
Aging Dis ; 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37450923

RESUMO

Various diseases, including cancers, age-associated disorders, and acute liver failure, have been linked to the oncogene, MYC. Animal testing and clinical trials have shown that sustained tumor volume reduction can be achieved when MYC is inactivated, and different combinations of therapeutic agents including MYC inhibitors are currently being developed. In this review, we first provide a summary of the multiple biological functions of the MYC oncoprotein in cancer treatment, highlighting that the equilibrium points of the MYC/MAX, MIZ1/MYC/MAX, and MAD (MNT)/MAX complexes have further potential in cancer treatment that could be used to restrain MYC oncogene expression and its functions in tumorigenesis. We also discuss the multifunctional capacity of MYC in various cellular cancer processes, including its influences on immune response, metabolism, cell cycle, apoptosis, autophagy, pyroptosis, metastasis, angiogenesis, multidrug resistance, and intestinal flora. Moreover, we summarize the MYC therapy patent landscape and emphasize the potential of MYC as a druggable target, using herbal medicine modulators. Finally, we describe pending challenges and future perspectives in biomedical research, involving the development of therapeutic approaches to modulate MYC or its targeted genes. Patients with cancers driven by MYC signaling may benefit from therapies targeting these pathways, which could delay cancerous growth and recover antitumor immune responses.

4.
Food Chem ; 402: 134068, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36126570

RESUMO

Steam-processed Polygonatum sibiricum (PS) has been used as food for thousands of years. However, fewer studies concentrated on the effects of polysaccharides (SPSP) from the steamed PS on the intestinal tract. With fermentation in vitro, we investigated the impact of SPSP on the fatty acids and microbiotas. Results showed significant increases in short-chain fatty acids (SCFAs) like acetic acid and propionic acid, and long-chain fatty acids (LCFAs) like cis, cis, cis-9,12,15-linolenic acid, cis-6-octadecenoic acid, and cis-9-octadecenoic acid after 12 h. The positive-associated beneficial microbiotas were observed with proliferation like Parabacteroides and Bifidobacterium. Harmful microbiota like Shigella showed decreased abundance. Further, a small molecule polysaccharide was separated from the SPSP with the structure of one glucose and ten fructose, which significantly increased SCFAs and LCFAs contents during fermentation. The potential benefits of SPSP were proved by the analysis of fatty acid levels and the intestinal microbiotas during fermentation.


Assuntos
Microbioma Gastrointestinal , Polygonatum , Polygonatum/química , Propionatos/farmacologia , Vapor , Ácido Oleico/farmacologia , Polissacarídeos/química , Glucose/química , Ácidos Graxos Voláteis , Frutose , Ácidos Linolênicos
5.
Environ Pollut ; 304: 119141, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35301029

RESUMO

Fumonisin B1 (FB1) is a neurodegenerative mycotoxin synthesized by Fusarium spp., but the potential neurobehavioral toxicity effects in organisms have not been characterized clearly. Caenorhabditis elegans (C. elegans) has emerged as a promising model organism for neurotoxicological studies due to characteristics such as well-functioning nervous system and rich behavioral phenotypes. To investigate whether FB1 has neurobehavioral toxicity effects on C. elegans, the motor behavior, neuronal structure, neurotransmitter content, and gene expression related with neurotransmission of C. elegans were determined after exposed to 20-200 µg/mL FB1 for 24 h and 48 h, respectively. Results showed that FB1 caused behavioral defects, including body bends, head thrashes, crawling distance, mean speed, mean amplitude, mean wavelength, foraging behavior, and chemotaxis learning ability in a dose-, and time-dependent manner. In addition, when C. elegans was exposed to FB1 at a concentration of 200 µg/mL for 24 h and above 100 µg/mL for 48 h, the GABAergic and serotonergic neurons were damaged, but no effect on dopaminergic, glutamatergic, and cholinergic neurons. The relative content of GABA and serotonin decreased significantly. Furthermore, abnormal expression of mRNA levels associated with GABA and serotonin were found in nematodes treated with FB1, such as unc-30, unc-47, unc-49, exp-1, mod-5, cat-1, and tph-1. The neurobehavioral toxicity effect of FB1 may be mediated by abnormal neurotransmission of GABA and serotonin. This study provides useful information for understanding the neurotoxicity of FB1.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Fumonisinas , Serotonina , Transmissão Sináptica , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/metabolismo , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/farmacologia , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/farmacologia
6.
Langmuir ; 38(4): 1560-1566, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35061400

RESUMO

Liquid crystal elastomers (LCEs) with large deformation under external stimuli have attracted extensive attention in various applications such as soft robotics, 4D printing, and biomedical devices. However, it is still a great challenge to reduce the damage to collimation and enhance the mechanical and actuation properties of LCEs simultaneously. Here, we construct a new method of a double cross-linking network structure to improve the mechanical properties of LCEs. The ureidopyrimidinone (UPy) group with quadruple hydrogen bonds was used as the physical cross-linking unit, and pentaerythritol tetra(3-mercaptopropionate) was used as the chemical cross-link. The LCEs showed a strong mechanical tensile strength of 8.5 MPa and excellent thermally induced deformation (50%). In addition, the introduction of quadruple hydrogen bonds endows self-healing ability to extend the service life of LCEs. This provides a generic strategy for the fabrication of high-strength LCEs, inspiring the development of actuators and artificial muscles.


Assuntos
Elastômeros , Cristais Líquidos , Elastômeros/química , Ligação de Hidrogênio , Cristais Líquidos/química , Resistência à Tração
7.
PhytoKeys ; 180: 53-64, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34393576

RESUMO

Parainvolucrella R.J. Wang, a new monotypic genus for P.scabra (Wall. ex Kurz) M.D.Yuan & R.J.Wang, new combination, is segregated from the Hedyotis-Oldenlandia complex, based on morphological and molecular evidence. Phylogenetically, the new genus is sister to Scleromitrion, from which it differs by a combination of morphological characters: herbaceous habit, terminal inflorescence with subtended leaves, heterostylous flowers, indehiscent fruits and pollen with double microreticulate tectum. A key to the genera of the Hedyotis-Oldenlandia complex in China is provided for further identification.

8.
J Med Chem ; 62(12): 5885-5900, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31125222

RESUMO

In this paper, we applied a chemotype-assembly approach for ligand-based drug discovery (LBDD) to discover novel anti-osteoporosis leads. With this new approach, we identified 12 chemotypes and derived 18 major chemotype assembly rules from 245 known anti-osteoporosis compounds. Then, we selected 19 compounds from an in-house compound library using chemotype-assembly approach for anti-osteoporosis assays, which resulted in 13 hits. Based on structural features in these 13 compounds, we synthesized 50 possible anti-osteoporosis compounds from the anti-osteoporosis chemotypes by means of click chemistry techniques and discovered a compound (10a, IC50 = 2 nM) with nanomolar activity. Compound 10a was then proved to be an anti-osteoporosis lead since it can prevent bone loss in vivo.


Assuntos
Descoberta de Drogas , Osteoporose/tratamento farmacológico , Animais , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/complicações , Reabsorção Óssea/prevenção & controle , Feminino , Fêmur/efeitos dos fármacos , Fêmur/fisiopatologia , Ensaios de Triagem em Larga Escala , Ligantes , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Osteoporose/complicações , Osteoporose/patologia , Osteoporose/fisiopatologia , Ratos , Ratos Sprague-Dawley
9.
iScience ; 11: 388-397, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30660106

RESUMO

We report here a supercatalyst for oxygen reduction of Pt/CNx/Ni in a unique ternary heterostructure, in which the Pt and the underlying Ni nanoparticles are separated by two to three layers of nitrogen-doped carbon (CNx), which mediates the transfer of electrons from the inner Ni to the outer Pt and protects the Ni against corrosion at the same time. The well-engineered low-Pt catalyst shows ∼780% enhanced specific mass activity or 490% enhanced specific surface activity compared with a commercial Pt/C catalyst toward oxygen reduction. More importantly, the exceptionally strong tune on the Pt by the unique structure makes the catalyst superbly stable, and its mass activity of 0.72 A/mgPt at 0.90 V (well above the US Department of Energy's 2020 target of 0.44 A/mgPt at 0.90 V) after 50,000 cyclic voltammetry cycles under acidic conditions is still better than that of the fresh commercial catalyst.

10.
Int Immunopharmacol ; 66: 19-27, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30419450

RESUMO

Astilbin (AST), a dihydro-flavonol glycoside, is a major bioactive ingredient in Astilbe thunbergii, Engelhardia roxburghiana, Smilax corbularia and Erythroxylum gonocladum, and has been shown to have anti-inflammatory, antioxidative and neuroprotective effects, suggesting potential therapeutic value in the treatment of Parkinson's disease (PD). We explored the neuroprotective effects of AST in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mice. Mice were administered with MPTP (30 mg/kg, i.p) daily for 5 days, to establish a subacute Parkinson's disease model, followed by daily treatment with AST or saline for 7 days. Pole and traction tests showed that AST ameliorated the impaired motor functions in MPTP-induced Parkinson's disease mice. High performance liquid chromatography analysis revealed that AST treatment prevented MPTP-induced decreases in striatal dopamine levels. Immunofluorescence assays showed that AST reduced the loss of dopaminergic neurons and the activation of microglia and astrocytes in the substantia nigra. Western blot analyses revealed that AST suppressed α-synuclein overexpression and activated PI3K/Akt in the striatum following MPTP treatment. AST also prevented the MPTP-induced reduction in total superoxide dismutase and glutathione activity in the striatum. AST exerts neuroprotective effects on MPTP-induced PD mice by suppressing gliosis, α-synuclein overexpression and oxidative stress, suggesting that AST could serve as a therapeutic drug to ameliorate PD.


Assuntos
Astrócitos/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Flavonóis/uso terapêutico , Intoxicação por MPTP/tratamento farmacológico , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Astrócitos/metabolismo , Astrócitos/patologia , Modelos Animais de Doenças , Neurônios Dopaminérgicos/fisiologia , Regulação para Baixo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/patologia , Atividade Motora , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Substância Negra/patologia , alfa-Sinucleína/metabolismo
11.
Nanoscale ; 10(46): 21944-21950, 2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30444229

RESUMO

The catalysts towards the oxygen reduction reaction (ORR) are the key materials for fuel cells and have stimulated continuous investigations on rational designs. Apart from the popular strategies reported, we demonstrate here a facile method resulting in a nanocomposite composed of molybdenum carbide (Mo2C) nanoparticles embedded and buried in Fe-N-doped carbon nanolayers by directly pyrolyzing the mixture of Fe2(MoO4)3 and dicyandiamide. The underlying Mo2C donates electrons of higher energy to the exterior N-containing carbon nanolayers (NC) and strongly couples with the active sites induced by Fe in the NC layer, leading to significant improvement at half-wave potential with respect to the control sample without Mo2C. The catalyst as a whole exhibits a fairly good ORR performance comparable to commercial Pt/C. Moreover, the method is extremely simplified and the material shows better long-term stability and tolerance to the methanol crossover in comparison with Pt/C.

12.
Neuroreport ; 29(13): 1075-1083, 2018 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-29985188

RESUMO

Aucubin (AUC) is a major bioactive ingredient in Eucommia ulmoides, Plantain asiatica, and Aucuba japonica, and has been shown to exert anti-inflammatory, antioxidative, and neuroprotective effects. We explore the neuroprotective effects of AUC in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mice. Mice were administered MPTP (30 mg/kg) daily for 5 days, followed by treatment with AUC for 7 days. Measurement of dopamine levels was performed by high-performance liquid chromatography and tyrosine hydroxylase expression was assessed by western blot. Our results showed that AUC treatment improved mobility in the pole descent test and the traction test, and reduced the loss of dopaminergic neurons in MPTP-induced parkinsonian mice. AUC treatment rescued the decreased dopamine and tyrosine hydroxylase levels in the striatum of parkinsonian mice. Furthermore, AUC treatment reduced both microglia and astrocyte activation in the substantia nigra of parkinsonian mice. These findings suggest that AUC exerts neuroprotective effects, in part by reducing inflammation and preserving dopaminergic neurons. Possible protection mechanisms involved in MPTP-induced parkinsonian mice need to be clarified further.


Assuntos
Astrócitos/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Glucosídeos Iridoides/administração & dosagem , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Doença de Parkinson/metabolismo , Transtornos Parkinsonianos/metabolismo , Animais , Astrócitos/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Atividade Motora/efeitos dos fármacos , Doença de Parkinson/prevenção & controle , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo
13.
Brain Behav Immun ; 70: 48-60, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29471030

RESUMO

Parkinson's disease (PD) patients display alterations in gut microbiota composition. However, mechanism between gut microbial dysbiosis and pathogenesis of PD remains unexplored, and no recognized therapies are available to halt or slow progression of PD. Here we identified that gut microbiota from PD mice induced motor impairment and striatal neurotransmitter decrease on normal mice. Sequencing of 16S rRNA revealed that phylum Firmicutes and order Clostridiales decreased, while phylum Proteobacteria, order Turicibacterales and Enterobacteriales increased in fecal samples of PD mice, along with increased fecal short-chain fatty acids (SCFAs). Remarkably, fecal microbiota transplantation (FMT) reduced gut microbial dysbiosis, decreased fecal SCFAs, alleviated physical impairment, and increased striatal DA and 5-HT content of PD mice. Further, FMT reduced the activation of microglia and astrocytes in the substantia nigra, and reduced expression of TLR4/TNF-α signaling pathway components in gut and brain. Our study demonstrates that gut microbial dysbiosis is involved in PD pathogenesis, and FMT can protect PD mice by suppressing neuroinflammation and reducing TLR4/TNF-α signaling.


Assuntos
Transplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal/fisiologia , Doença de Parkinson/terapia , Animais , Encéfalo , Modelos Animais de Doenças , Disbiose/metabolismo , Disbiose/fisiopatologia , Fezes/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia , Neuroglia/efeitos dos fármacos , Fármacos Neuroprotetores , Doença de Parkinson/fisiopatologia , RNA Ribossômico 16S/genética , Receptor 4 Toll-Like/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
15.
Chemphyschem ; 18(23): 3454-3461, 2017 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-28906066

RESUMO

The development of low-cost non-precious-metal electrocatalysts with high activity and stability in the oxygen reduction reaction (ORR) remains a great challenge. Heteroatom-doped carbon materials are receiving increased attention in research as effective catalysts. However, the uncontrolled doping of heteroatoms into a carbon matrix tends to inhibit the activity of a catalyst. Here, the in situ activation of a uniquely structured nitrogen-doped carbon/Ni composite catalyst for the ORR is demonstrated. This well-designed catalyst is composed of a nitrogen-doped carbon shell and embedded metallic nickel. The embedded Ni nanoparticles, dispersed on stable alumina with a high specific surface area for protecting them from agglomeration and in an unambiguous composite structure, are electron-donating and are shielded by the nitrogen-doped carbon from oxidation/dissolution in harsh environments. The electronic structure of the nitrogen-doped carbon shell is modulated by the transfer of electrons at the interface of nitrogen-doped carbon-Ni heterojunctions owing to the Mott-Schottky effect. The electrochemically active surface area result implies that the active sites do not relate to Ni directly and the enhanced catalytic activity mainly arises from the modulation of nitrogen-doped carbon by nickel. XPS and theoretical calculations suggest that the donated electrons are transferred to pyridinic N primarily, which ought to enhance the catalytic activity intrinsically. Benefiting from these transferred electrons, the half-wave potential of the nitrogen-doped carbon/Ni composite catalyst is 94 mV positively shifted compared to the Ni-free sample.

16.
Biochem Biophys Res Commun ; 489(3): 275-280, 2017 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-28559136

RESUMO

Human spinal cord injury (SCI) usually causes irreversible disability beneath the injured site due to poor neural regeneration. On the contrary, zebrafish show significant regenerative ability after SCI, thus is usually worked as an animal model for studying neuroregeneration. Most of the previous SCI studies focused on the local site of SCI, the supraspinal-derived signals were rarely mentioned. Here we showed that intradiencephalon injection of histamine (HA) inhibited the locomotor recovery in adult zebrafish post-SCI. Immunofluorescence results showed that intradiencephalon HA administration increased the activated microglia 3 days post injury (dpi), promoted the proliferation of radial glial cells at 7 dpi and affected the morphology of radial glial cells at 11 dpi. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) results showed that intradiencephalon HA administration also reduced the expression of neurotrophic factors including brain-derived neurotrophic factor (BDNF) and insulin-like growth factor1 (IGF-1) at the lesion site, however, had no effect on the expression of pro-inflammatory factors such as TNF-alpha and IL-1 beta. Hence, our data suggested that exogenous intradiencephalon HA retarded locomotor recovery in spinal cord injured zebrafish via modulating the repair microenvironment.


Assuntos
Histamina/administração & dosagem , Histamina/farmacologia , Locomoção/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/fisiopatologia , Peixe-Zebra , Animais , Injeções Intraventriculares , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Traumatismos da Medula Espinal/patologia , Relação Estrutura-Atividade , Peixe-Zebra/fisiologia
17.
J Cell Biochem ; 118(10): 3495-3510, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28338241

RESUMO

Parkinson's disease (PD) is a progressive neurodegenerative disease, involving resting tremor and bradykinesia, for which no recognized therapies or drugs are available to halt or slow progression. In recent years, natural botanic products have been considered relatively safe, with limited side effects, and are expected to become an important source for clinical mediation of PD in the future. Our study focuses on the ability of loganin, a compound derived from fruits of cornus, to mediate neuroprotection in a mouse model of PD. Mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) with a dosage of 30 mg/kg daily for 5 days to establish a subacute PD model and treated with loganin. Locomotor activity was assessed by a pole test, then mice were euthanized at 1 and 3 days after the last treatment, and brain tissue was prepared for subsequent assays. Loganin rescued decrease of dopamine levels and tyrosine hydroxylase (TH) expression in the striatum, and shortened total locomotor activity (TLA) time of mice. Furthermore, loganin alleviated microglia and astrocyte activation, and suppressed TNF-α and caspase-3 expression through a c-Abl-p38-NFκB pathway. Loganin also downregulated LC3-II and Drp1 expression, and decreased the level of acidic vesicular organelles (AVOs). Loganin exerts neuroprotective effects on MPTP-induced PD mice by decreasing inflammation, autophagy, and apoptosis, suggesting that loganin could serve as a therapeutic drug to ameliorate PD. J. Cell. Biochem. 118: 3495-3510, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Astrócitos/metabolismo , Corpo Estriado/metabolismo , Iridoides/farmacologia , Intoxicação por MPTP/prevenção & controle , Microglia/metabolismo , Doença de Parkinson Secundária/prevenção & controle , Animais , Astrócitos/patologia , Corpo Estriado/patologia , Dopamina/metabolismo , Intoxicação por MPTP/metabolismo , Intoxicação por MPTP/patologia , Masculino , Camundongos , Microglia/patologia , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/metabolismo , Doença de Parkinson Secundária/patologia , Tirosina 3-Mono-Oxigenase/metabolismo
18.
J Cell Biochem ; 118(3): 615-628, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27662601

RESUMO

1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), which induces the pathological characteristics of Parkinson's disease in rodents, also specifically targets dopaminergic neurons in zebrafish embryos and larvae. Loganin, a traditional Chinese drug, was reported to regulate immune function and possess anti-inflammatory and anti-shock effects. Here, we investigate the role of loganin in MPTP-induced Parkinson-like abnormalities in zebrafish. MPTP treatment-induced abnormal development, in larvae, such as pericardium edema, increased yolk color, yolk sac edema, and retarded yolk sac resorption, as well as defects in brain development. Loganin could block MPTP-induced defects, with little toxicity to the eggs. Results of whole mount in situ hybridization showed loganin prevented the loss of both dopaminergic neurons and locomotor activity, exhibited by larvae treated with MPTP. In addition, loganin significantly rescued MPTP-induced neurotoxicity on PC12 cells, possibly through the suppression of PI3K/Akt/mTOR axis and JNK signaling pathways. In conclusion, loganin blocks MPTP-induced neurotoxicity and abnormal development in zebrafish. J. Cell. Biochem. 118: 615-628, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Iridoides/farmacologia , Intoxicação por MPTP/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Peixe-Zebra/embriologia , Animais , MAP Quinase Quinase 4/metabolismo , Intoxicação por MPTP/embriologia , Células PC12 , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Serina-Treonina Quinases TOR/metabolismo , Proteínas de Peixe-Zebra/metabolismo
19.
Phys Chem Chem Phys ; 12(34): 10027-32, 2010 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-20577678

RESUMO

Adenosine deaminase is an enzyme involved in purine metabolism and its inhibitors are used as anticancer and antiviral drugs. In this study, we show that fast-scan cyclic voltammetry at carbon-fiber microelectrodes can be used to study the kinetics of adenosine deaminase by electrochemically monitoring decreases in adenosine concentration. Buffer and salt concentrations were shown to affect the enzyme kinetics and the inhibition by erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and deoxycoformycin (DCF). In a Tris buffer containing salts that mimic cerebrospinal fluid, EHNA and DCF showed non-competitive inhibition with a K(i) of 1.7 +/- 0.6 nM and 1.2 +/- 0.2 nM, respectively. However, removing the divalent cations from the Tris buffer caused the inhibition to be competitive and reduced the K(i) for DCF by two orders of magnitude. In phosphate-buffered saline, the K(i) was 1.0 +/- 0.2 nM for EHNA and 3.6 +/- 0.3 pM for DCF, similar to literature values. Adenosine deaminase was also competitively inhibited by AgNO(3), showing it is susceptible to silver toxicity. Caffeine was found to increase adenosine deaminase activity. This is a fast, easy method for screening drug effects on enzyme kinetics and could be applied to other enzymatic reactions where there is a significant difference in the electroactivity of the reactant and product.


Assuntos
Adenosina Desaminase/metabolismo , Eletroquímica/métodos , Ensaios Enzimáticos/métodos , Adenina/análogos & derivados , Adenina/farmacologia , Adenosina , Inibidores de Adenosina Desaminase/farmacologia , Animais , Cafeína/farmacologia , Bovinos , Condutividade Elétrica , Cinética , Oxirredução , Pentostatina/farmacologia , Antagonistas de Receptores Purinérgicos P1/farmacologia , Receptores Purinérgicos P1/metabolismo , Prata/farmacologia , Fatores de Tempo
20.
Langmuir ; 25(1): 568-73, 2009 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-19067579

RESUMO

The operation of ion channel sensors is mimicked with functionalized polymeric membrane electrodes, using a surface confined affinity reaction to impede the electrochemically imposed ion transfer kinetics of a marker ion. A membrane surface biotinylated by covalent attachment to the polymeric backbone is used here to bind to the protein avidin as a model system. The results indicate that the protein accumulates on the ion-selective membrane surface, partially blocking the current-induced ion transfer across the membrane/aqueous sample interface, and subsequently decreases the potential jump in the so-called super-Nernstian step that is characteristic of a surface depletion of the marker ion. The findings suggest that such a potential drop could be utilized to measure the concentration of protein in the sample. Because the sensitivity of protein sensing is dependent on the effective blocking of the active surface area, it can be improved with a hydrophilic nanopore membrane applied on top of the biotinylated ion-selective membrane surface. On the basis of cyclic voltammetry characterization, the nanoporous membrane electrodes can indeed be understood as a recessed nanoelectrode array. The results show that the measuring range for protein sensing on nanopore electrodes is shifted to lower concentrations by more than 1 order of magnitude, which is explained with the reduction of surface area by the nanopore membrane and the related more effective hemispherical diffusion pattern.


Assuntos
Canais Iônicos/química , Mimetismo Molecular , Polímeros/química , Potenciometria/métodos , Proteínas/análise
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